Despite well-documented successes in earlier detection of breast cancer, age-adjusted death rates have improved marginally in recent years. One postulated reason for this failure to effect more dramatic improvement in outcome is that tumor cell dissemination occurs very early, negating much of the survival advantage of early diagnosis. Recognition of early dissemination in many patients has forced clinical oncologists and surgeons to rethink the general philosophy of treatment of breast cancer. Effective application of individualized therapy will eventually require more precise identification of patients at high risk for local recurrence and distant metastasis (Visscher et al., Pathology Annual 25:171-210, 1990).
Cell proliferation is a necessary step for tumor development. Not surprisingly, cell proliferation indices have been shown to be prognosis-related (Munro Diagn Oncol 1:53-63, 1991). However, several problems limit today techniques that estimate cell proliferation (Visscher et al. Op. cit.). Prothymosin alpha expression has been shown to be associated with cell division (Rosen et al., Histochemistry 94:597-599, 1990) pointing to the fact that prothymosin alpha could play a basic role in normal cell division that is also conserved in tumor cells. Until now, all of the known cell proliferation indices have several problems that limit their effective application in the precise identification of patients at high risk for local recurrence and distant metastasis.